Lipopolysaccharide-Induced Model of Neuroinflammation: Mechanisms of Action, Research Application and Future Directions for Its Use

Molecules, Journal Year: 2022, Volume and Issue: 27(17), P. 5481 - 5481

Published: Aug. 26, 2022

Despite advances in antimicrobial and anti-inflammatory therapies, inflammation its consequences still remain a significant problem medicine. Acute inflammatory responses are responsible for directly life-threating conditions such as septic shock; on the other hand, chronic can cause degeneration of body tissues leading to severe impairment their function. Neuroinflammation is defined an response central nervous system involving microglia, astrocytes, cytokines including chemokines. It considered important neurodegerative diseases, Alzheimer's disease, Parkinson's disease amyotrophic lateral sclerosis. Lipopolysaccharide (LPS) strong immunogenic particle present outer membrane Gram-negative bacteria. major triggering factor cascade bacteria infection. The use LPS pro-inflammatory agent well-known model applied both vivo vitro studies. This review offers summary pathogenesis associated with exposure, especially field neuroinflammation. Moreover, we analyzed different models utilized area neuroscience. paper presents recent knowledge focused new insights experimental model.

Language: Английский

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The role of Toll-like receptors and neuroinflammation in Parkinson’s disease

Journal of Neuroinflammation, Journal Year: 2022, Volume and Issue: 19(1)

Published: June 6, 2022

Abstract Background Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder, characterized by motor and non-motor symptoms, significantly affecting patients’ life. Pathologically, PD associated with extensive degeneration of dopaminergic neurons in various regions central nervous system (CNS), specifically substantia nigra. This neuronal loss accompanied aggregation misfolded protein, named α-synuclein. Main text Recent studies detected several clues neuroinflammation samples using postmortem human brains animal models. Some evidence patients included higher levels proinflammatory cytokines serum cerebrospinal fluid (CSF), presence activated microglia brain such as nigra, infiltration peripheral inflammatory cells affected regions, altered function cellular immunity like monocytes phagocytosis defects. On other side, Toll-like receptors (TLRs) are innate immune primarily located on microglia, well non-immune cells, expressing pivotal roles recognizing exogenous endogenous stimuli triggering responses. Most indicated an increased expression TLRs blood samples. Besides, this upregulation was excessive followed neurodegeneration regions. Therefore, proposed that TLR-mediated might lead to a neural patients. In regard, TLR2, TLR4, TLR9 have prominent roles. Conclusion Although inflammation acute phases protective effects concerning clearance α-synuclein delaying advancement, chronic activation neurodegeneration, resulting progression. study aimed review additional contribution pathogenesis, hope could serve novel disease-modifying therapeutic targets future.

Language: Английский

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Modulation of the Innate Immune Response by Targeting Toll-like Receptors: A Perspective on Their Agonists and Antagonists

Journal of Medicinal Chemistry, Journal Year: 2020, Volume and Issue: 63(22), P. 13466 - 13513

Published: Aug. 26, 2020

Toll-like receptors (TLRs) are a class of proteins that recognize pathogen-associated molecular patterns (PAMPs) and damaged-associated (DAMPs), they involved in the regulation innate immune system. These transmembrane receptors, localized at cellular or endosomal membrane, trigger inflammatory processes through either myeloid differentiation primary response 88 (MyD88) TIR-domain-containing adapter-inducing interferon-β (TRIF) signaling pathways. In last decades, extensive research has been performed on TLR modulators their therapeutic implication under several pathological conditions, spanning from infections to cancer, metabolic disorders neurodegeneration autoimmune diseases. This Perspective will highlight recent discoveries this field, emphasizing role TLRs different diseases effect natural synthetic modulators, it discuss insights for future exploitation human health.

Language: Английский

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Biodegradable Hollow‐Structured Nanozymes Modulate Phenotypic Polarization of Macrophages and Relieve Hypoxia for Treatment of Osteoarthritis

Small, Journal Year: 2022, Volume and Issue: 18(32)

Published: July 17, 2022

Abstract Nanozymes are widely applied for treating various major diseases, including neurological diseases and tumors. However, the biodegradability of nanozymes remains a great challenge, which hinders their further clinical translation. Based on microenvironment osteoarthritis (OA), representative pH‐responsive biodegradable hollow‐structured manganese Prussian blue nanozyme (HMPBzyme) is designed treatment OA. HMPBzyme with good biodegradability, biocompatibility, multi‐enzyme activities constructed by bovine serum albumin bubbles as template‐mediated biomineralization strategy. suppresses hypoxia‐inducible factor‐1α (HIF‐1α) expression decreases reactive oxygen species (ROS) level in vitro experiment. Furthermore, markedly ROS alleviates degeneration cartilage OA rat models. The results indicate that inhibits oxidative damage relieves hypoxia synergistically to suppress inflammation promote anabolism extracellular matrix protecting mitochondrial function down‐regulating HIF‐1α, modulates phenotypic conversion macrophages from pro‐inflammatory M1 subtype anti‐inflammatory M2 treatment. This research lays solid foundation design, construction, biomedical application promotes biomedicine.

Language: Английский

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Function and inhibition of P38 MAP kinase signaling: Targeting multiple inflammation diseases

Biochemical Pharmacology, Journal Year: 2023, Volume and Issue: 220, P. 115973 - 115973

Published: Dec. 14, 2023

Language: Английский

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Inhibition of CDK4/6 regulates AD pathology, neuroinflammation and cognitive function through DYRK1A/STAT3 signaling

Pharmacological Research, Journal Year: 2023, Volume and Issue: 190, P. 106725 - 106725

Published: March 11, 2023

Repurposing approved drugs is an emerging therapeutic development strategy for Alzheimer's disease (AD). The CDK4/6 inhibitor abemaciclib mesylate FDA-approved drug breast cancer treatment. However, whether affects Aβ/tau pathology, neuroinflammation, and Aβ/LPS-mediated cognitive impairment unknown. In this study, we investigated the effects of on function pathology found that improved spatial recognition memory by regulating dendritic spine number neuroinflammatory responses in 5xFAD mice, Aβ-overexpressing model AD. Abemaciclib also inhibited Aβ accumulation enhancing activity protein levels Aβ-degrading enzyme neprilysin α-secretase ADAM17 decreasing level γ-secretase PS-1 young aged mice. Importantly, suppressed tau phosphorylation mice tau-overexpressing PS19 reducing DYRK1A and/or p-GSK3β levels. wild-type (WT) injected with lipopolysaccharide (LPS), rescued restored number. addition, downregulated LPS-induced microglial/astrocytic activation proinflammatory cytokine WT BV2 microglial cells primary astrocytes, LPS-mediated downregulating AKT/STAT3 signaling. Taken together, our results support repurposing anticancer drug, as a multitarget AD pathologies.

Language: Английский

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Ketogenic diet alleviates cognitive dysfunction and neuroinflammation in APP/PS1 mice via the Nrf2/HO-1 and NF-κB signaling pathways

Neural Regeneration Research, Journal Year: 2023, Volume and Issue: 18(12), P. 2767 - 2772

Published: May 12, 2023

Alzheimer's disease is a progressive neurological disorder characterized by cognitive decline and chronic inflammation within the brain. The ketogenic diet, widely recognized therapeutic intervention for refractory epilepsy, has recently been proposed as potential treatment variety of diseases, including disease. However, efficacy diet in treating underlying mechanism remains unclear. current investigation aimed to explore effect on function biological mechanisms mouse model Male amyloid precursor protein/presenilin 1 (APP/PS1) mice were randomly assigned either or control group, received their respective diets duration 3 months. findings show that administration enhanced function, attenuated plaque formation proinflammatory cytokine levels APP/PS1 mice, augmented nuclear factor-erythroid 2-p45 derived factor 2/heme oxygenase-1 signaling pathway while suppressing factor-kappa B pathway. Collectively, these data suggest may have ameliorating neurotoxicity associated with Aβ-induced inflammation. This study highlights urgent need further research into use therapy

Language: Английский

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The Role of Intestinal Microbiota and Diet as Modulating Factors in the Course of Alzheimer’s and Parkinson’s Diseases

Nutrients, Journal Year: 2024, Volume and Issue: 16(2), P. 308 - 308

Published: Jan. 19, 2024

Many researchers propose manipulating microbiota to prevent and treat related diseases. The brain-gut axis is an object that remains the target of modern research, it not without reason many enrich with diet in its name. Numerous connections mutual correlations have become basis for seeking answers questions pathology as well human physiology. Disorders this homeostasis dysbiosis itself accompany neurodegenerative diseases such Alzheimer's Parkinson's. Heavily dependent on external factors, modulation gut microbiome represents opportunity advance treatment Probiotic interventions, synbiotic or fecal transplantation can undoubtedly support biotherapeutic process. A special role played by diet, which provides metabolites directly affect body microbiota. holistic view organism therefore essential.

Language: Английский

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The Impact of Microbiota–Immunity–Hormone Interactions on Autoimmune Diseases and Infection

Biomedicines, Journal Year: 2024, Volume and Issue: 12(3), P. 616 - 616

Published: March 8, 2024

Autoimmune diseases are complex multifactorial disorders, and a mixture of genetic environmental factors play role in their onset. In recent years, the microbiota has gained attention as it helps to maintain host health immune homeostasis is relevant player interaction between our body outside world. Alterations (dysbiosis) its composition or function have been linked different pathologies, including autoimmune diseases. Among functions, there activation/modulation cells that can protect against infections. However, if dysbiosis occurs, compromise host’s ability pathogens, contributing development progression some cases, infections trigger by several mechanisms, alteration gut permeability activation innate produce pro-inflammatory cytokines recruit autoreactive T B cells. this scenario, we cannot neglect critical hormones’ roles regulating responses. Different hormones, especially estrogens, shown influence modulating activity system ways. review, summarized main mechanisms connection infections, microbiota, immunity, hormones diseases’ onset given hormone levels on pathogenesis. detail, focused rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus.

Language: Английский

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Recent advances in osteoarthritis research: A review of treatment strategies, mechanistic insights, and acupuncture

Medicine, Journal Year: 2025, Volume and Issue: 104(4), P. e41335 - e41335

Published: Jan. 24, 2025

Osteoarthritis (OA) is a chronic joint condition affecting millions worldwide, characterized by the gradual degeneration of cartilage, leading to pain, stiffness, and functional impairment. Although pathogenesis OA not fully understood, roles inflammation, metabolic dysregulation, biomechanical stress are increasingly recognized. Current treatments, including pharmacotherapy, physical therapy, surgical interventions, aim alleviate symptoms improve quality life, yet they face limitations challenges. In recent years, researchers have explored variety new treatment strategies, such as molecular targeted biologic regenerative medicine, lifestyle modifications, aiming directly address root causes complex mechanisms OA. This review aims summarize latest research advancements provide fresh perspectives for clinical lay foundation future development strategies

Language: Английский

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